!! Intracerebral hemorrhage (ICH) is a stroke subtype with high mortality and patients who survive have major neurological deficits. Mass effect and release of hematoma components are two key factors causing brain injury following ICH. Many clinical trials have examined the effect of clot removal, but surgical evacuation has not been shown to be beneficial. Studies have demonstrated that hemolysis in the hematoma occurs the first day after ICH and erythrocyte lysis has a role in ICH- induced brain injury. Peroxiredoxin-2 is the third most abundant protein in red blood cells; peroxiredoxins are key initiators of brain inflammation after stroke. In our preliminary studies, we have also demonstrated: 1) Peroxiredoxin-2 levels are increased in the perihematomal zone after ICH; 2) Intra-caudate injection of peroxiredoxin-2 causes brain swelling, neuronal death and neurological deficits; 3) Conoidin A, an inhibitor of peroxiredoxins, reduces lysed red blood cell-induced brain swelling, neuronal loss and neurological deficits. In this application, therefore, we propose to test the following Specific Aims: 1) to examine natural history of peroxiredoxin-2 accumulation in the brain in an aged rat model of ICH; 2) to determine whether exogenous/extracellular peroxiredoxin-2 causes brain injury and neurological deficits; 3) to determine the effects of peroxiredoxin inhibition on ICH- induced brain damage. The purpose of our project is to determine the role of peroxiredoxin-2, a major protein in red blood cells, in ICH-induced brain injury. The long-term goal of our study is to limit hemorrhagic brain damage and to improve functional outcome in patients. !